Luiza Moraes Holst, Jonas Halfvarson, Marie Carlson, Charlotte Hedin, Robert Kruse, Carl Mårten Lindqvist, Daniel Bergemalm, Sven Almér, Francesca Bresso, Maria Ling Lundström, Dirk Repsilber, Mauro D'Amato, Åsa Keita, Henrik Hjortswang, Johan Söderholm, Johanna Sundin, Hans Törnblom, Magnus Simrén, Hans Strid, Maria K Magnusson, Lena Öhman
{"title":"活性和静止性溃疡性结肠炎中下调的粘膜自噬、α激酶-1和IL-17信号通路","authors":"Luiza Moraes Holst, Jonas Halfvarson, Marie Carlson, Charlotte Hedin, Robert Kruse, Carl Mårten Lindqvist, Daniel Bergemalm, Sven Almér, Francesca Bresso, Maria Ling Lundström, Dirk Repsilber, Mauro D'Amato, Åsa Keita, Henrik Hjortswang, Johan Söderholm, Johanna Sundin, Hans Törnblom, Magnus Simrén, Hans Strid, Maria K Magnusson, Lena Öhman","doi":"10.2147/CEG.S368040","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohn's disease (CD active).</p><p><strong>Methods: </strong>Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways.</p><p><strong>Results: </strong>The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed.</p><p><strong>Conclusion: </strong>This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares.</p>","PeriodicalId":10208,"journal":{"name":"Clinical and Experimental Gastroenterology","volume":" ","pages":"129-144"},"PeriodicalIF":2.5000,"publicationDate":"2022-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343467/pdf/","citationCount":"2","resultStr":"{\"title\":\"Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis.\",\"authors\":\"Luiza Moraes Holst, Jonas Halfvarson, Marie Carlson, Charlotte Hedin, Robert Kruse, Carl Mårten Lindqvist, Daniel Bergemalm, Sven Almér, Francesca Bresso, Maria Ling Lundström, Dirk Repsilber, Mauro D'Amato, Åsa Keita, Henrik Hjortswang, Johan Söderholm, Johanna Sundin, Hans Törnblom, Magnus Simrén, Hans Strid, Maria K Magnusson, Lena Öhman\",\"doi\":\"10.2147/CEG.S368040\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohn's disease (CD active).</p><p><strong>Methods: </strong>Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways.</p><p><strong>Results: </strong>The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed.</p><p><strong>Conclusion: </strong>This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares.</p>\",\"PeriodicalId\":10208,\"journal\":{\"name\":\"Clinical and Experimental Gastroenterology\",\"volume\":\" \",\"pages\":\"129-144\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2022-07-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343467/pdf/\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Experimental Gastroenterology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2147/CEG.S368040\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Experimental Gastroenterology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2147/CEG.S368040","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis.
Background: Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohn's disease (CD active).
Methods: Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways.
Results: The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed.
Conclusion: This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares.